CD44 antigen isoform v6 (CD44v6)

CD44 antigen isoform v6 (CD44v6) is a specific splice variant of the CD44 transmembrane glycoprotein, distinguished by the inclusion of the v6 exon in its extracellular domain. It functions as a crucial co-receptor for several receptor tyrosine kinases, most notably c-Met and VEGFR-2, and is required for their efficient activation and subsequent intracellular signaling pathways like Ras-MAPK. While CD44v6 expression is limited in normal adult tissues—primarily found in some squamous epithelia—it is frequently overexpressed in various solid tumors, including head and neck, lung, and colorectal cancers, where it correlates with increased metastatic potential and poor prognosis. Therapeutically, CD44v6 has been targeted using monoclonal antibodies and antibody-drug conjugates (ADCs) to deliver cytotoxic agents directly to tumor cells. However, clinical development has faced challenges due to severe dermatological toxicities resulting from target expression in normal skin keratinocytes. Despite these challenges, it remains a significant biomarker for cancer stem cells and a focus for developing safer, more localized therapeutic interventions.

Other names

CD44 variant 6CD44v6EpicanHeparan sulfate proteoglycanPhagocytic glycoprotein 1 isoform v6Extracellular matrix receptor IIIGP90 lymphocyte homing/adhesion receptor

Monoclonal antibody binding to the v6-encoded domain to inhibit receptor-ligand interaction and downstream signaling; delivery of cytotoxic payloads via antibody-drug conjugates (ADCs); peptide-mediated inhibition of co-receptor function for c-Met and VEGFR-2.